组合配体策略在铁催化烷烃碳氢氮宾插入反应中的应用研究——从反应活性到不对称催化

氮杂环结构广泛存在于药物化学和天然产物中，发展其高效的合成方法具有重要的意义。铁催化直接碳氢氮宾插入反应是合成该结构的最有效方法之一，然而现有方法主要依赖于来源有限的卟啉铁和酞菁铁催化剂。本课题拟研究组合配体策略在铁催化碳氢氮宾插入反应中的应用， 希望发展一个简单、高效、高选择性的方法，同时深入研究催化剂的作用机理和发展高效的不对称催化体系。具体包括：1)研究三齿和二齿氮配体组合和铁前体形成的络合物的催化活性、机理和构效关系，发展出一种高活性的铁催化剂能够实现对烷烃C(sp3)–H的氮宾插入；2)研究该策略的底物应用范围，拓展铁催化碳氢氮宾插入反应的底物类型到氨基磺酰胺和磺酰胺类底物，并应用在一些重要分子的后期修饰和manzacidin A的合成之中；3)使用手性配体的组合，实现铁催化的不对称氮宾插入反应，研究催化剂手性传递机制。

It is of significant impacts to develop efficient methods for the synthesis of nitrogen-containing heterocycles since they are prevalent in natural products and pharmaceuticals. Iron-catalyzed intramolecular C–H nitrene insertion is among the most direct and useful methods, however, the reported catalysts primarily reply on the use of very source-limited porphyrino- and phthalocyaninato-iron complexes. The proposed project is to develop a combinatorial iron catalysis strategy applicable in C–H nitrene insertion and investigate the mechanism of this process. We hope the iron catalysts derived from simple and readily available ligands could enable both racemic and enantioselective iron-nitreniod insertion chemistry, which includes: 1) studying the activities of the complexes derived from the combination of tridentate, bidentate ligands and iron precursors in iron-nitreniod insertion reaction of inert C(sp3)–H bonds, the mechanism of the reaction, and the structure-activity relationship of the catalysts; 2) applying the combinatorial iron catalysis in aliphatic substrates to expand the scope to sulfonamides and sulfamides, late stage modification of bio-important molecules, and the synthesis of manzacidin A；3) developing asymmetric iron-nitreniod insertion system by the combination of chiral ligands and understand the stereocontrol mechanism.